Silver(I)-mediated base pairing in DNA involving the artificial nucleobase 7,8-dihydro-8-oxo-1,N6-ethenoadenine.

ABSTRACT

The artificial nucleobase 7,8-dihydro-8-oxo-1,N6-ethenoadenine (X) was investigated with respect to its ability to engage in Ag(I)-mediated base pairing in DNA. Spectroscopic data indicate the formation of dinuclear X-Ag(I)2-X homo base pairs and mononuclear X-Ag(I)-C base pairs (C, cytosine). Density functional theory calculations and molecular dynamics simulations indicate that the nucleobase changes from its lactam tautomeric form prior to the formation of the Ag(I)-mediated base pair to the lactim form after the incorporation of the Ag(I) ions. Fluorescence spectroscopy indicates that the two Ag(I) ions of the homo base pair are incorporated sequentially. Isothermal titration calorimetry confirms that the affinity of one of the Ag(I) ions is about tenfold higher than that of the other Ag(I) ion. The computational analysis by means of density functional theory confirms a much larger reaction energy for the incorporation of the first Ag(I) ion. The thermal stabilization upon the formation of the dinuclear Ag(I)-mediated homo base pair exceeds the one previously observed for the closely related nucleobase 1,N6-ethenoadenine by far, despite very similar structures. This additional stabilization may stem from the presence of water molecules engaged in hydrogen bonding with the additional oxygen atom of the artificial nucleobase X. The highly stabilizing Ag(I)-mediated base pair is a valuable addition to established dinuclear metal-mediated base pairs.